Autonomic Pharmacology (book) Flashcards
the nervous system can be divided into two major subdi- visions:
autonomic and somatic
is largely independent in that its activities are not under direct conscious control
autonomic nervous system
concerned primarily with control and integration of visceral functions necessary for life such as cardiac output, blood flow distribution, and digestion.
autonomic nervous system
largely concerned with consciously controlled functions such as movement, respiration, and posture.
somatic
Chemical transmission takes place through the release of small amounts of ____ from the nerve terminals into the synaptic cleft.
transmitter substances
The ANS lends itself to division on anatomic grounds into two major portions:
the sympathetic (thoracolumbar) division and the parasympathetic (traditionally “craniosacral,”
The sympathetic preganglionic fibers leave the CNS through the
thoracic, lumbar, and sacral spinal nerves
The parasympathetic preganglionic fibers leave the CNS through the
cranial nerves
*especially the third, seventh, ninth, and tenth
Most thoracic and lumbar sympathetic preganglionic fibers are short and terminate in ganglia located in the __ chains that lie on either side of the spinal column.
paravertebral
Most of the remaining sympathetic preganglionic fibers are somewhat longer and termi- nate in ___, which lie in front of the vertebrae, usually on the ventral surface of the aorta.
prevertebral ganglia
Some preganglionic parasympathetic fibers terminate in parasympathetic ganglia located outside the organs innervates:
the ciliary, pterygopalatine, submandibular, and otic ganglia.
Several pelvic ganglia are innervated by ___ that are ontogenetically similar to sympathetic preganglionic fibers
sacral preganglionic nerves
A large and highly orga- nized collection of neurons located in the walls of the gastrointes- tinal (GI) system
enteric nervous system (ENS)
The ENS includes the
myenteric plexus (the plexus of Auerbach) and the submucous plexus (the plexus of Meissner)
The primary transmitter at ANS ganglia, at the somatic neuromuscular junction, and at parasympathetic postganglionic nerve endings.
Acetylcholine (ACh)
A primary excitatory transmitter to smooth muscle and secretory cells in the ENS. Probably also the major neuron-to-neuron (“ganglionic”) transmitter in the ENS.
Acetylcholine
Acts as a transmitter or cotransmitter at many ANS-effector synapses
Adenosine triphosphate (ATP)
Found with substance P in cardiovascular sensory nerve fibers. Present in some secretomotor ENS neurons and interneurons. A cardiac stimulant
Calcitonin gene-related peptide (CGRP)
May act as a cotransmitter in some excitatory neuromuscular ENS neurons
Cholecystokinin (CCK)
A modulatory transmitter in some ganglia and the ENS. Possibly a postganglionic sympathetic transmitter in renal blood vessels
Dopamine
Present in some secretomotor and interneurons in the ENS. Appear to inhibit ACh release and thereby inhibit peristalsis. May stimulate secretion
Enkephalin and related opioid peptides
Present in secretomotor neurons; may play a role in appetite-satiety mechanisms
Galanin
May have presynaptic effects on excitatory ENS nerve terminals. Has some relaxant effect on the gut. Prob- ably not a major transmitter in the ENS
GABA (γ-aminobutyric acid)
Extremely potent excitatory transmitter to gastrin cells. Also known as mammalian bombesin
Gastrin-releasing peptide (GRP)
Found in many noradrenergic neurons. Present in some secretomotor neurons in the ENS and may inhibit secretion of water and electrolytes by the gut.
Neuropeptide Y (NPY)
Causes long-lasting vasoconstriction. It is also a cotransmitter in some parasympathetic postganglionic neurons
Neuropeptide Y (NPY)
A cotransmitter at inhibitory ENS and other neuromuscular junctions; may be especially important at sphinc- ters
Nitric oxide (NO)
The primary transmitter at most sympathetic postganglionic nerve endings
Norepinephrine (NE)
An important transmitter or cotransmitter at excitatory neuron-to-neuron junctions in the ENS
Serotonin (5-HT)
an important sensory neurotransmitter in the ENS and elsewhere. Tachykinins appear to be excitatory cotransmitters with ACh at ENS neuromuscular junctions. Found with CGRP in cardiovascular sen- sory neurons.
Substance P, related tachykinins
Excitatory secretomotor transmitter in the ENS; may also be an inhibitory ENS neuromuscular cotransmitter. A probable cotransmitter in many cholinergic neurons. A vasodilator (found in many perivascular neurons) and cardiac stimulant.
Vasoactive intestinal peptide (VIP)
A large number of peripheral ANS fibers synthesize and release acetylcholine; they are ___ fibers; that is, they work by releasing acetylcholine
cholinergic
Most postganglionic sympathetic fibers release norepinephrine (also known as noradrenaline); they are __
noradrenergic/adrenergic
primary acetylcholine receptor subtypes
muscarinic and nicotinic receptors
receptors that respond to catecholamines
adrenoceptor
receptors (both muscarinic and nicotinic) that respond to acetylcholine
cholinoceptor
The general class of adrenoceptors can be further subdivided into
α-adrenoceptor, β-adrenoceptor, and dopamine-receptor
a neurotoxin derived from chili peppers
Capsaicin
The sensory fibers in the nonadrenergic, noncholinergic sys- tems are probably better termed
“sensory-efferent” or “sensory- local effector” fibers
when activated by a sensory input, they are capable of releasing transmitter peptides from the sensory ending itself, from local axon branches, and from collaterals that terminate in the autonomic ganglia.
sensory fibers in the nonadrenergic, noncholinergic sys- tems
___ sensory fibers in the wall of the urinary bladder significantly influence sympathetic inhibitory outflow to that organ
parasympathetic
the primary controlled variable in cardiovascular function is ____.
mean arterial pressure
_____ is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT)
Choline
sodium-dependent choline transporter (CHT) can be inhibited by ___ drugs
hemicholinium
In the cytoplasm, acetylcholine is synthesized from ___ and ___ by the enzyme choline acetyltransferase (ChAT).
choline and acetyl-CoA (AcCoA)
Acetylcholine (ACh) is transported into the storage vesicle by a ____, which can be inhibited by ___
vesicle-associated transporter (VAT)
vesamicol
Release of transmitters occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of ___
calcium
The resulting increase in intracellular calcium causes ___ and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft
fusion of vesicles with the surface membrane
[The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft]
This step can be blocked by ___
botulinum toxin
Acetylcholine’s action is terminated by metabolism by the enzyme ___.
acetylcholinesterase
___ is transported into the noradrenergic nerve ending or varicosity by a sodium-dependent carrier
Tyrosine
Tyrosine is converted to ___, and transported into
the vesicle by the vesicular monoamine transporter (VMAT), which can be blocked by __ and __
dopamine
reserpine and tetrabenazine
Dopamine is converted to ___ in the vesicle by dopamine-β-hydroxylase
NE
Fusion of vesicles with the surface membrane results in expulsion of ___
Release can be blocked by drugs such as ___ and ___
norepinephrine, cotransmitters, and dopamine-β-hydroxylase.
guanethidine and bretylium
After release, norepinephrine diffuses out of the cleft or is transported into the cytoplasm of the terminal by the ____, which can be blocked by ___ and certain antidepressants, or into postjunctional or perijunctional cells.
norepinephrine transporter (NET)
cocaine
Increased baroreceptor activity causes the ___ central sympathetic outflow and ___ vagal outflow.
decreased
increased
Presynaptic receptors that respond to the primary transmitter substance released by the nerve ending are called __
autoreceptors
Postsynaptic regulation can be considered from two perspectives:
modulation by previous activity at the primary receptor
modulation by other simultaneous events
An extreme form of upregulation occurs after denervation of some tissues, resulting in ___ of the tissue to activators of that receptor type.
denervation supersensitivity
Drugs that block action potential propagation are very ___ in their action, since they act on a process that is common to all neurons.
nonselective
drugs that act on the biochemical processes involved in transmitter synthesis and storage are more ___
selective
*since the biochemistry of each transmitter differs, eg, norepinephrine synthesis is very different from acetyl- choline synthesis.
Parasympathetic nerve activity and muscarinic cholinomimetics mediate ___ of the circular pupillary constrictor muscle and of the ciliary muscle
contraction
Contraction of the pupillary constrictor muscle causes ___
miosis
*a reduction in pupil size
Acetylcholine-receptor stimulants and cholinesterase inhibitors make up a large group of drugs that mimic ___
acetylcholine
mimicked the effects of parasympathetic nerve discharge
muscarine
The effects of acetylcholine itself and of other cholinomimetic drugs at autonomic neuroeffector junctions are called ___ and are mediated by __ receptors.
parasympathomimetic effects
muscarinic
Cholinoceptors are members of either ___ on the basis of their structure and transmembrane signaling mechanisms.
G protein-linked (muscarinic) or ion channel (nicotinic) families
Muscarinic receptors contain ___ transmembrane domains whose third cytoplasmic loop is coupled to __ that function as transducers
seven
G proteins
___ cholinomimetic agents bind to and activate mus- carinic or nicotinic receptors
Direct-acting
___ agents produce their primary effects by inhibiting acetylcholinesterase, which hydrolyzes acetylcholine to choline and acetic acid
Indirect-acting
direct-acting cholinomimetic drugs can be divided on the basis of chemical structure into
esters of choline (including acetyl- choline) and alkaloids (such as muscarine and nicotine).
Choline esters are poorly absorbed and poorly distributed into the central nervous system because they are __
hydrophilic
Nicotine, a liquid, is sufficiently ___ to be absorbed across the skin
lipid-soluble
are well absorbed from the skin, lung, gut, and conjunctiva—thereby making them dangerous to humans and highly effective as insecticides.
organophosphate cholinesterase inhibitors (except for echothiophate)
The fatal dose of nicotine is approximately ___mg, or 1 drop of the pure liquid.
40 mg
M1 receptor subtype is located on
central nervous system (CNS) neurons
autonomic postganglionic cell bodies
presynaptic sites
M2 receptors are located in the
myocardium
smooth muscle organs
some neuronal sites
M3 receptors are most common on ___
effector cell membranes
*especially glandular and smooth muscle cells
Muscarinic antagonists are sometimes called ___ because they block the effects of parasympathetic autonomic discharge.
parasympatholytic
Atropine causes reversible blockade of ___ actions at muscarinic receptors
cholinomimetic
